Socioeconomic disadvantage is associated with a greater likelihood of being diagnosed with cancer, delays in cancer diagnosis, receiving less treatment, decreased access to palliative care and hospice services, and increased mortality. Although interventions have been developed to reduce the incidence of cancer and delays in diagnosis in those from socioeconomically disadvantaged backgrounds; few interventions exist to improve access to palliative care and hospice services for individuals with the least resources and greatest needs for these services. The NIH consensus statement on cancer-related symptoms concluded that the most common and debilitating are depression, pain and fatigue. Our team has observed that people from socioeconomically disadvantaged backgrounds with advanced cancer have disproportionately higher levels of depression, pain and fatigue and poorer quality of life than patients who reported higher socioeconomic status (SES). Although the comorbidity of these symptoms is well known, no intervention has been developed to reduce these symptoms concurrently. Experience from our successful pilot study of a web-based stepped collaborative care intervention for cancer patients from predominantly socioeconomically disadvantaged backgrounds, revealed that patients randomized to the intervention arm, reported statistically significant reductions in depression, pain, and fatigue an improved quality of life when compared to patients randomized to enhanced usual care (K07CA118576). Furthermore, patients randomized to the intervention had decreased serum levels of Interleukin (IL)-1?, IL-6, IL-8 and improved survival (R21CA127046). Post-hoc analyses revealed that family caregivers, of patients randomized to the intervention arm, had reductions in stress and depression, when compared to caregivers with spouses/partners randomized to enhanced usual care (K07CA118576S1). There is an urgent need to develop scalable, effective, and, cost-effective interventions, particularly for those who are socioeconomically disadvantaged. We plan to test a web-based stepped collaborative care intervention with 450 advanced cancer patients and their spousal or intimate partners in the context of a randomized controlled trial. The specific aims are: (1) to test the efficacy of a web-based stepped collaborative care intervention to reduce symptoms of depression, pain, and fatigue and improve health-related quality of life (HRQL) in advanced cancer patients when compared to patients randomized to the education and support arm; (2) to examine if advanced cancer patients randomized to the web-based stepped collaborative care intervention have reductions in biomarkers of inflammation and explore if these patients have slowed disease progression and improved survival when compared to patients in the education and support arm; (3) to investigate whether the spouses or intimate partners, of patients randomized to the web-based stepped collaborative care intervention, have reduced stress and depression, better HRQL and fewer risk factors for CVD than caregivers with spouses/partners randomized to education and support arm. In accordance with the goals of Healthy People 2020 to achieve health equity, eliminate disparities, and improve the health of all groups, regardless of differences that occur by gender, race or ethnicity, education or income, disability, geographic location, or sexual orientation this proposed web-based stepped collaborative care intervention was designed to improve HRQL for those in greatest need and least access to palliative care. This innovative and scalable web-based stepped collaborative care intervention is expected to improve patients' and caregivers' HRQL and potentially reduce mortality. Findings are expected to lead to studies examining scalability and cost-effectiveness of the proposed intervention.